Search PubMed⌕ Search

Biomedical subjects

Michael Chan

Publications and source records attributed to Michael Chan.

13 recordsLinked to original sources
PubMed2006

Synthesis and immunostimulatory activity of 8-substituted amino 9-benzyladenines as potent Toll-like receptor 7 agonists.

Several 9-benzyl adenine derivatives bearing various substituted amines at the 8-position have been prepared and evaluated for interferon induction in peripheral blood mononuclear cells (PBMC) from healthy human donors. The 8-bromoadenine derivative 5 was used as a versatile intermediate for all substitutions. The most active 8-substituted amino compound was found to be the 8-morpholinoethylamino derivative 19 which had an EC(50) in the submicromolar range.

Adenine↗
PubMed2006

Activation of anti-hepatitis C virus responses via Toll-like receptor 7.

IFN-alpha is used to suppress the replication of hepatitis C virus (HCV) in chronically infected patients with partial success. Here we present evidence showing that a ligand of Toll-like receptor 7 (TLR7) can induce anti-HCV immunity not only by IFN induction, but also through an IFN-independent mechanism. Human hepatocyte line Huh-7 carrying an HCV replicon expressed TLR7, and activation of the receptor induced several antiviral genes including IFN regulatory factor-7. Inhibitors of the enzyme inosine monophosphate dehydrogenase augmented both IFN-dependent and -independent antiviral effect. Prolonged exposure of Huh-7 cells to a TLR7 ligand [SM360320 (9-benzyl-8-hydroxy-2-(2-methoxyethoxy)adenine)], alone or in combination with an inosine monophosphate dehydrogenase inhibitor, reduced HCV levels dose dependently. Immunohistochemical analysis of livers shows that TLR7 is expressed in hepatocytes of normal or HCV-infected people. Because TLR7 agonists can impede HCV infection both via type I IFN and independently of IFN, they may be considered as an alternative treatment of chronic HCV infection, especially in IFN-alpha-resistant patients.

Adenine↗
PubMed2006

Coronary air embolism: a case report and review of the literature.

Coronary air embolism is a complication in the catheterization laboratory that can be associated with high morbidity and even mortality. A case report of air embolism and methods to prevent this complication from occurring are presented along with various management techniques.

Aged↗
PubMed2006

Radiology curriculum topics for medical students: students' perspectives.

RATIONALE AND OBJECTIVE: We sought to establish medical students' perspectives of a set of curriculum topics for radiology teaching. MATERIALS AND METHODS: A multicenter study was conducted in New Zealand. A modified Delphi method was adopted. Students enrolled in two New Zealand Universities received a questionnaire. Each learning topic was graded on a scale of 1 (very strongly disagree) to 6 (very strongly agree). Students could also put forward and grade suggestions that were not on the questionnaire. RESULTS: Of 200 questionnaires, 107 were returned. Fifty male and 57 female students participated, with an average age of 23.7 years. The five highest ranking curriculum topics in order of importance were developing a system for viewing chest radiographs (5.77, SD 0.7), developing a system for viewing abdominal radiographs (5.66, SD 0.8), developing a system for viewing bone and joint radiographs (5.56, SD 0.8), distinguishing normal structures from abnormal in chest and abdominal radiographs (5.38, SD 0.9), and identifying gross bone or joint abnormalities in skeletal radiographs (5.29, SD 0.9). CONCLUSION: Medical students want to know how to look at radiographs, how to distinguish normal from abnormal, and how to identify gross abnormalities.

Adult↗
PubMed2006

The effectiveness of passive stretching in children with cerebral palsy.

Passive stretching is widely used for individuals with spasticity in a belief that tightness or contracture of soft tissues can be corrected and lengthened. Evidence for the efficacy of passive stretching on individuals with spasticity is limited. The aim of this review was to evaluate the evidence on the effectiveness of passive stretching in children with spastic cerebral palsy. Seven studies were selected according to the selection criteria and scored against the Physiotherapy Evidence Database scale. Effect size and 95% confidence intervals were calculated for comparison. There was limited evidence that manual stretching can increase range of movements, reduce spasticity, or improve walking efficiency in children with spasticity. It appeared that sustained stretching of longer duration was preferable to improve range of movements and to reduce spasticity of muscles around the targeted joints. Methods of passive stretching were varied. Further research is required given the present lack of knowledge about treatment outcomes and the wide use of this treatment modality.

Cerebral Palsy↗
PubMed2006

Catheter-induced coronary artery dissection: risk factors, prevention and management.

Guide catheter-induced dissection of the coronary arteries is an uncommon but potentially catastrophic complication of diagnostic and interventional cardiac catheterization. Several factors placing the individual at higher risk of this complication have been identified. We discuss these risk factors and utilize them to propose methods to prevent dissections. Management options of coronary artery dissection are also discussed.

Aortic Dissection↗
PubMed2005

Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis improves cholesterol profile in heart transplant recipients with treated but persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus vs cyclosporine microemulsion.

BACKGROUND: Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported. METHODS: One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.5 mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio >4 were recruited for the study. Complete lipid profile was assessed before (baseline) and after 6 months of treatment with either cyclosporine microemulsion maintenance (n=64) or tacrolimus conversion (n=65). RESULTS: At 6 months, tacrolimus-converted patients exhibited a greater decrease in total cholesterol (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to 5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in cholesterol was caused largely by a decrease in low-density lipoprotein cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine]; p=0.0018). There were no changes in high-density lipoprotein cholesterol and triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus-converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus resulted in decreases in blood urea nitrogen, creatinine, and uric acid without any changes in glucose, HbA(1C), and insulin levels. CONCLUSIONS: Conversion from cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without any clinically evident perturbation of glucose metabolism in stable heart transplant recipients with treated but persistent mild dyslipidemia.

Adult↗
PubMed2005

Extremely rare glioblastoma multiforme of the conus medullaris with holocord and brain stem metastases, leading to cranial nerve deficit and respiratory failure: a case report and review of the literature.

BACKGROUND: Spinal glioblastoma multiforme (GBM) is an uncommon entity and metastases are extremely rare. Glioblastoma multiforme of the conus medullaris is a rare and highly aggressive entity that can quickly progress to a dismal state. Proper diagnosis via histopathologic and immunochemical staining with close clinical and radiological follow-up is important for the management of this very aggressive tumor. CASE DESCRIPTION: The authors report the clinical features, histopathologic and immunochemical staining characteristics, as well as the radiographic evidence of a case of primary GBM of the conus medullaris with metastases to the whole spinal cord and brain in a 20-year-old man who presented with low back pain and bilateral lower extremity weakness and numbness. Review of the pathology slides using histopathologic and immunochemical staining showed GBM. Serial magnetic resonance scans, performed after the initial surgery, demonstrated enlargement of the primary GBM in the conus medullaris with metastases to the thoracic and cervical spinal cord as well as to the brain. CONCLUSIONS: Glioblastoma multiforme of the conus medullaris with such clinical findings is extremely rare. We analyze similar cases in the literature and discuss the importance of monitoring the progression of such an entity as well as the need for aggressive management of the different complications as they arise to maintain a good quality of life.

Adult↗
PubMed2005

Modeling intercellular interactions during carcinogenesis.

By modulating the microenvironment of malignant or premalignant cells, inhibitory or stimulatory signals from nearby cells can play a key role in carcinogenesis. However, current commonly used quantitative models for induction of cancers by ionizing radiation focus on single cells and their progeny. Intercellular interactions are neglected or assumed to be confined to unidirectional radiation bystander effect signals from cells of the same tissue type. We here formulate a parsimoniously parameterized two-stage logistic (TSL) carcinogenesis model that incorporates some effects of intercellular interactions during the growth of premalignant cells. We show that for baseline tumor rates, involving no radiation apart from background radiation, this TSL model gives acceptable fits to a number of data sets. Specifically, it gives the same baseline hazard function, using the same number of adjustable parameters, as does the commonly used two-stage clonal expansion (TSCE) model, so it is automatically applicable to the many data sets on baseline cancer that have been analyzed using the TSCE model. For perturbations of baseline rates due to radiation, the models differ. We argue from epidemiological and laboratory evidence, especially results for the atomic bomb survivors, that for radiation carcinogenesis the TSL model gives results at least as realistic as the TSCE or similar models, despite involving fewer adjustable parameters in many cases.

Carcinogenicity Tests↗
PubMed2003

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults.

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.

Action Potentials↗
PubMed2002

Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by a two-amino-acid insertion in HIV-1 Vif from a nonprogressing mother and child.

We studied a 15-year-old girl, patient X, who has maintained consistently low plasma loads of human immunodeficiency virus type 1 (HIV-1) RNA, as well as normal and stable CD4(+) T-cell concentrations. She has presented no clinical manifestations of AIDS, despite having only received zidovudine monotherapy for a part of her life. Patient X's HIV-positive mother (patient Y) has also not progressed to AIDS and has never been treated with antiretroviral agents. HIV-1 isolated from patient X replicated poorly in human peripheral blood mononuclear cells (PBMC). In order to map the determinant of the poor growth of patient X's isolate, viral sequences from patient X were determined and examined for insertion or deletion mutations. These sequences contained a two-amino-acid insertion mutation in the Vif gene, which was also observed in uncultured PBMC acquired at different times. Furthermore, Vif sequences harbored by patient Y contained the identical mutation. These observations suggest that polymorphic HIV-1 was transmitted to patient X perinatally 15 years previously and has been maintained since that time. Recombinant HIV-1, engineered with Vif sequences from patient X, replicated in PBMC to levels approximately 20-fold lower than that of wild type. Removal of the insertion mutation from this recombinant restored replication efficiency to wild-type levels, while introduction of the insertion mutation into wild-type Vif sequences resulted in greatly decreased replication. Furthermore, Vif protein from patient X's HIV-1 was aberrantly cleaved, suggesting a mechanism for loss of Vif function. Since HIV-1 containing these sequences replicates poorly, the implication is that the two-amino-acid insertion mutation in Vif contributes significantly to the nonprogressor status of this mother and child. Further studies of these sequences might provide information regarding contributions of Vif structure and/or function to HIV-1 virulence.

Adolescent↗